Platelet-derived growth factor-BB enhances MSC-mediated cardioprotection via suppression of miR-320 expression

American Journal of Physiology. Heart and Circulatory Physiology
Bing XuYue Wang

Abstract

Delivery of bone marrow-derived mesenchymal stem cells (MSCs) to myocardium protects ischemic tissue through the paracrine release of beneficial angiogenic and cytoprotective factors. Platelet-derived growth factor (PDGF)-BB, a potent mitogen of MSCs, is involved in the pathophysiology of ischemic heart disease. However, the role(s) of PDGF in MSC-mediated cardioprotection remains unknown. Here, we found that PDGF treatment of MSCs resulted in rapid activation of both Akt and ERK (central intracellular signal mediators), upregulated VEGF, and induced phosphorylation of the activator protein-1 (AP-1) transcription factor c-Jun. Examination of several microRNA genes having predicted promoter c-Jun-binding sites showed that PDGF treatment resulted in upregulation of miR-16-2 and downregulation of miRs-23b, -27b, and -320b. To examine possible PDGF augmentation of therapeutic potential, we evaluated the effects of PDGF using an ex vivo isolated mouse heart ischemia-reperfusion model. Human MSCs, with or without PDGF preconditioning, were infused into the coronary circulation of isolated mouse hearts. The hearts that received PDGF-treated MSCs exhibited a greater functional recovery compared with naïve MSC-infused hearts, following ...Continue Reading

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Citations

Apr 14, 2016·Oxidative Medicine and Cellular Longevity·Xinchun YeGuiyun Cui
Dec 19, 2015·Stem Cells International·Liangpeng LiChunyu Zeng
Apr 18, 2018·Tissue Engineering. Part a·Siddharth PatelLuiz E Bertassoni
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May 9, 2019·Stem Cells International·Changming XieHui Huang
Nov 7, 2015·Stem Cell Research & Therapy·Jie ChengHongbing Jiang
Nov 30, 2019·BioMed Research International·Cheng JuZhiping Zhang

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